The main objective of the proposed research is to elucidate the mechanisms of action of pharmacological agents on neuromuscular junctions. Special emphases are placed on the effects of these drugs on postsynaptic membranes as examined by the use of microelectrode and voltage clamp techniques. Changes in chemical sensitivity and membrane potential of the end-plate as affected by depolarization and non-depolarizing blocking agents are to be analyzed in terms of ionic permeabilities of the membrane. Desensitization of the end-plate membrane in the continuous presence of depolarizing blocking agents is interpreted at the level of membrane ionic permeabilities. Certain depolarizing end-plate blocking agents have been found in our previous study to exert a non-depolarizing blocking action at concentrations insufficient for depolarization. In view of the critical importance of this dual action, detailed experiments are performed to elucidate the mechanisms in terms of ionic permeabilities and voltage and time dependency. This study is expected to open a road to the molecular mechanisms of drug action and to provide the basis for improvement of therapeutic agents.